Bladder cancer is the second most common genitourinary tumor, having an incidence of approximately 357,000 new cases each year worldwide (Parkin D M, et al., Cancer J Clin 2005 55:74-108). Approximately one third of them are suspected to be invasive or metastatic disease at the time of diagnosis (NPL 1-3). Although radical cystectomy for invasive bladder cancer remains the standard of treatment in many parts of the world, nearly half of such patients develop metastases within two years after cystectomy and subsequently die of the disease. In the last two decades cisplatin-based combination chemotherapy regimens, such as CMV (cisplatin, methotrexate, and vinblastine) or M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin), have been prescribed for patients with advanced bladder cancers (NPL 3-6). However, the overall prognosis still remains very poor and adverse reactions caused by these combination chemotherapies are significantly severe (NPL 7). Therefore, development of a new molecular target drug(s) against bladder cancer is desired earnestly.
With that goal in mind, the present inventors previously analyzed the gene-expression profiles of 26 bladder cancers and 29 normal human tissues (NPL 8,9), and identified a gene and corresponding peptide designed DEP domain containing 1 (DEPDC1) that was highly up-regulated in the great majority of bladder cancer cells, but not expressed in normal human organs except testis, indicating this molecule to be a novel cancer/testis antigen (PTL 1). This data further suggested that DEPDC1 could serve as a valuable target for development of anti-cancer agents or cancer peptide-vaccines for bladder cancer (PTL 2). Further research demonstrated that suppression of DEPDC1 expression with small-interfering RNA (siRNA) significantly inhibited growth of bladder cancer cells. Although the data to date suggests that DEPDC1 plays a critical role in the growth and/or survival of bladder cancer, its molecular mechanism remains unknown.